Synthesis of Silyl Alcohols

In this section the unsaturated silyl alcohols are classified based on the relative position of hydroxyl group to mono unsaturation and the total sum of unsaturations. For example enyne is with C=C and C=C and allenene is C=C=C and C=C in a silyl alcohol molecule. 

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Table 24.24. Stereoselective synthesis of silyl alcohols and diendiynes [1]...

The hydrosilylation of carbonyl compounds by EtjSiH catalysed by the copper NHC complexes 65 and 66-67 constitutes a convenient method for the direct synthesis of silyl-protected alcohols (silyl ethers). The catalysts can be generated in situ from the corresponding imidazolium salts, base and CuCl or [Cu(MeCN) ]X", respectively. The catalytic reactions usually occur at room tanperature in THE with very good conversions and exhibit good functional group tolerance. Complex 66, which is more active than 65, allows the reactions to be run under lower silane loadings and is preferred for the hydrosilylation of hindered ketones. The wide scope of application of the copper catalyst [dialkyl-, arylalkyl-ketones, aldehydes (even enoUsable) and esters] is evident from some examples compiled in Table 2.3 [51-53],... 

Scheme 3.34. Intermolecular domino radical addition procedure for the synthesis of silyl-protected allylic alcohols.

Doyle and co-workers have employed Rh2(pfb)4 as a highly selective catalyst for the room temperature synthesis of silyl ethers from alcohols and triethylsilane.159 The selectivity of the catalyst is demonstrated by reactions of olefinic alcohols, in which hydrosilylation is not competitive with silane alcoholysis when equimolar amounts of silane and alcohol are employed. High yields (>85%) of triethylsilyl ethers are obtained from reactions of alcohols such as benzyl alcohol, 1-octanol, 3-buten-l-ol, cholesterol, and phenol. Tertiary alcohols are not active in this system. 

Thus far we have been using (+)-ethyl lactate as the alcohol in the first step in the synthesis of silyl ketals. As we mentioned in the introduction, in order for our method to be transferred for use with high-value synthetic intermediates in a complex target-oriented synthesis, we must explore the scope and limitation of our method. We began by evaluating the synthesis of silyl ketals by reversing the order of the alcohol addition (Scheme 30). 

Admixture of alkynylstannanes, aldehydes, trimethylsilyl chloride, and InClj in acetonitrile at room temperature results in the formation of propargyl silyl ethers. In the synthesis of homoallylic alcohols, simple allylic halides can be used to form the tin halides in situ in water. ... 

Regiospecific nucleophilic ring opening of oxetanes to 3-silyl-oxyisocyanides with trimethylsilyl cyanide/Znl2 in dichloromethane has been reported, and this has led to the synthesis of amino-alcohols by hydrolysis of the isocyanide group. ... 

Applications Based on a-Lithio-selenoxides. Full details have appeared on the uses of cf-lithio-selenoxides, generated by low-temperature deprotonation of selenoxides with LDA. They are probably less nucleophilic than the corresponding cf-lithio-selenides. Their reactions leading to olefins, allylic alcohols, and (less well explored) enones are summarized in Scheme 15, and they have also been applied in the synthesis of silyl enol ethers (Scheme 16). 

The synthesis of the alcohol 8 started with protection of known homoallyUc alcohol 10 as its MPM ether and subsequent cleavage of the double bond to give the aldehyde 11 (Scheme 2). Roush asymmetric crotylation of 11 by using chiral crotyl boronate 12 provided the alcohol 13. Silylation of 13 followed by removal of the MPM group led to the alcohol 14, which was inverted via Mitsunobu reaction to afford the alcohol 8. Here we intentionally used the homoallylic alcohol 10 with incorrect configuration as the starting material and synthesized 8 in a circuitous manner. This was because asymmetric crotylation of ent-11, which we initially tried, only provided the alcohol 15 as an inseparable 1 1 mixture of diastereomers. 

Silyl ethers serve as preeursors of nucleophiles and liberate a nucleophilic alkoxide by desilylation with a chloride anion generated from CCI4 under the reaction conditions described before[124]. Rapid intramolecular stereoselective reaction of an alcohol with a vinyloxirane has been observed in dichloro-methane when an alkoxide is generated by desilylation of the silyl ether 340 with TBAF. The cis- and tru/u-pyranopyran systems 341 and 342 can be prepared selectively from the trans- and c/.y-epoxides 340, respectively. The reaction is applicable to the preparation of 1,2-diol systems[209]. The method is useful for the enantioselective synthesis of the AB ring fragment of gambier-toxin[210]. Similarly, tributyltin alkoxides as nucleophiles are used for the preparation of allyl alkyl ethers[211]. 

Silylated cyanohydrins have also been prepared via silylation of cyanohydrins themselves and by the addition of hydrogen cyanide to silyl enol ethers. Silylated cyanohydrins have proved to be quite useful in a variety of synthetic transformations, including the regiospecific protection of p-quinones, as intermediates in an efficient synthesis of a-aminomethyl alcohols, and for the preparation of ketone cyanohydrins themselves.The silylated cyanohydrins of heteroaromatic aldehydes have found extensive use as... 

The sluggishness of the reaction of TIPSOTf with tertiary alcohols can be exploited to advantage, as was the case in Magnus synthesis of strychnine. The equilibrium favors the tertiary hemiketal, but silylation favors the primary alcohol. 

Schemes 28 and 29 illustrate Curran s synthesis of ( )-hirsutene [( )-1]. Luche reduction58 of 2-methylcyclopentenone (137), followed by acetylation of the resulting allylic alcohol, furnishes allylic acetate 138. Although only one allylic acetate stereoisomer is illustrated in Scheme 28, compound 138 is, of course, produced in racemic form. By way of the powerful Ireland ester enolate Clai-sen rearrangement,59 compound 138 can be transformed to y,S-unsaturated tm-butyldimethylsilyl ester 140 via the silyl ketene acetal intermediate 139. In 140, the silyl ester function and the methyl-substituted ring double bond occupy neighboring regions of space, a circumstance that favors a phenylselenolactonization reac-...

Scheme 5 details the asymmetric synthesis of dimethylhydrazone 14. The synthesis of this fragment commences with an Evans asymmetric aldol condensation between the boron enolate derived from 21 and trans-2-pentenal (20). Syn aldol adduct 29 is obtained in diastereomerically pure form through a process which defines both the relative and absolute stereochemistry of the newly generated stereogenic centers at carbons 29 and 30 (92 % yield). After reductive removal of the chiral auxiliary, selective silylation of the primary alcohol furnishes 30 in 71 % overall yield. The method employed to achieve the reduction of the C-28 carbonyl is interesting and worthy of comment. The reaction between tri-n-butylbor-... 

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